Since the 1973 description by Broviac of his use of the silicone catheter that now bears his name [Broviac J W, et al., Surg Gynecol Obstet 136:602-606, 1973], tunnelled central venous catheters and ports have played pivotal roles in making advances in survival possible for children with cancer and for those requiring hyperalimentation, hemodialysis, or exchange transfusion. Although surgically-implanted vascular catheters have been essential in enabling the care of such children, our patients continue—even in 2012—to be vexed by catheter-related bloodstream infections. In pediatric oncology, catheter-related bloodstream infections remain the most common cause of nosocomial infection [Simon A., et al., Infect Control Hosp Epidemiol 21:592-6, 2000]. Following the recent declaration by the Centers for Medicaid Services that hospital-acquired catheter-related bloodstream infections may result in reductions or elimination of reimbursement to hospitals [Federal Register, available at www.federalregister.gov/articles/2011/06/06/2011-13819/medicaid-program-payment-adjustment-for-provider-preventable-conditions-including-health#p-69, accessed Feb. 26, 2012], the urgency of the problem is now peaking rather than diminishing.
Numerous strategies have been advanced to combat catheter-related bloodstream infections in children, including insertion checklists, which are useful at the time of catheter insertion but do not address decontamination over extended time periods [Pronovost P, et al., N Engl J Med 355:2725-2732, 2006]; instillation of antibiotic-locks, which carry the spectre of fostering resistant organisms [Smith T L, et al.: N Engl J Med 340:493-501, 1999]; and instillation of clot-dissolving substances such as urokinase, which may actually lead to bacteremia [La Quaglia M P, et al., J Pediatr Surg 29(6):742-745, 1994]. To date, no heparin-compatible, prophylactic solution exists that is suitable for pediatric administration and carries both antibacterial and antifungal activities. A promising recent development, however, has been the intraluminal use of ethanol.
Ethanol-locking strategies in pediatrics have gained traction following a 2003 retrospective report by Dannenberg et al. in which 18 pediatric patients with Broviac catheters were treated with a 74% ethanol solution that was allowed to dwell in the catheter lumen for 20-24 hours and then flushed through [Dannenberg C, et al., J Pediatr Hematol Oncol 25(8):616-621, 2003]. This technique appeared to help treat refractory infections and did not seem to cause any symptoms in children. Others went on to find that ethanol did not appear to damage silicone catheters at the concentrations used [Crnich C J, et al., Infect Control Hosp Epidemiol 26:708-714, 2005].
Building on such retrospective reports, one of the present inventors ran the first prospective, pediatric clinical trial to study safety and blood alcohol levels among children receiving ethanol-lock therapy four times a week [Kayton M L, et al., J Pediatr Surg 45:1961-1966, 2010]. Blood alcohol levels were indeed all below the “legal limit” of 80 mg/dL. However, the study was voluntarily terminated after 123 ethanol-lock administrations, but prior to full patient accrual, when an undue incidence of catheter occlusion was noted. This was serious enough in 3 of the 12 patients studied to warrant return to the operating room, including in one patient whose device fractured and embolized after flushing the catheter against a solid obstruction of the lumen. Catheter thrombosis following ethanol-lock administration has been reported in several other trials now that the use of ethanol has become more widespread [Wales P W, et al., J Pediatr Surg 46:951-956, 2011; Mouw E, et al., J Pediatr Surg 43:1025-1029, 2008]. As a result, many pediatric oncologists and surgeons now shy away from ethanol-lock use as prophylaxis, fearing loss of the very catheter they wish to preserve; ethanol-locks are generally used as a late salvage maneuver in the setting of refractory infection.